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What is Bevacizumab?

Bevacizumab is a medication used in the treatment of certain types of cancers. It is sold under the brand name Avastin. This medication is often used along with chemotherapy to prevent further growth of the tumor cells. 

Bevacizumab is known as an anti-vascular endothelial growth factor monoclonal antibody. Vascular Endothelial Growth Factor (VEGF) is a signaling protein that helps form blood vessels in the body. Blood supply is essential for cells to grow and multiply as it provides oxygen and nutrients. By acting as an anti-VEGF antibody, the medication starves the cancer cells and prevents their growth.

This is a biological medication (made from living organisms) approved by the US FDA (Food and Drug Administration). It is currently used as a first and second-line treatment option for colorectal cancers and as a first-line treatment option for non-small cell lung cancer.

Bevacizumab is also used to treat renal cell carcinoma, ovarian cancer, severe glioblastoma (tumor affecting the spine and brain), and advanced cervical cancer. 

Bevacizumab In Breast Cancer Treatment 

In 2008, the US FDA approved bevacizumab to treat metastatic (cancer that spreads from the primary location to other organs) HER2-negative breast cancer. In 2011 though, the FDA removed the medicine from the list of approved drugs for treating breast cancer.

According to the FDA, the potential side-effects and risks of this medication were much higher than its effect on breast cancer. They argued that bevacizumab only slightly increased the cancer-free period and did not increase the overall survival rate.

Though the medication has been removed from the approved drug list, doctors can still use it for breast cancer treatment with the patient’s approval.

How Does Bevacizumab Cause Hypertension?

There are many side effects of using Bevacizumab, and one such significant risk is bevacizumab-induced hypertension. Hypertension is consistently high blood pressure over 140/90. 

Three theories explain how bevacizumab usage can cause hypertension. 

Nitric Oxide (NO) Theory

NO is a molecule that is produced by almost all types of cells in the human body. NO helps the blood vessels relax and prevents high blood pressure. Studies show that reduced VEGF activity because of bevacizumab causes a decrease in the production of NO. Low NO levels lead to an increase in blood pressure. 

Many experts support this theory because, in most patients, the blood pressure normalizes once they stop receiving Bevacizumab. 

Kidney Impairment Theory

VEGF proteins are essential for the growth and maturation of the glomerular network in the kidneys. These are groups of small blood vessels located at the beginning of all the nephrons of the kidneys. The glomerular network filters the blood before it reaches the nephrons.

VEGF inhibition leads to abnormalities in the growth and maturation of the glomerular structure. This can lead to a condition called proteinuria. Proteinuria is the presence of excess proteins in urine. 

Certain studies report that people with proteinuria have a higher risk of developing hypertension.  

Pre-eclampsia-like Theory

Pre-eclampsia is a pregnancy complication that leads to high blood pressure. In pregnant women with pre-eclampsia, low VEGF levels are noted. As a result, this theory states that VEGF inhibition may be one reason for pre-eclampsia and, therefore, hypertension. 

A 2010 meta-analysis published in the American Journal of Hypertension analyzed the relationship between bevacizumab therapy and hypertension. The analysis looked at 20 studies and a total of 12,656 cancer patients. According to the study, people treated with bevacizumab had a higher risk of developing high blood pressure.


Another meta-analysis studied the relationship between bevacizumab and hypertension in 72 clinical trials involving 21,900 patients. According to the study, 25.3% of these patients developed hypertension, and 8.2% had grade 3 and grade 4 hypertension.

A different meta-analysis analyzed the prevalence of hypertension in 3155 non-small cell lung cancer patients. The study reported that 19.55% of people developed hypertension after being treated with bevacizumab, and 6.95% developed high-grade hypertension. 

How Does Genetics Influence Bevacizumab-induced Hypertension?

The SV2C Gene

The SV2C gene (Synaptic Vesicle Glycoprotein 2C gene) produces the SV2C protein. It plays a role in the normal functioning of the neural and endocrine cells and helps in low-frequency neurotransmission. 

rs2059157 is a Single Nucleotide Polymorphism or SNP in the SV2C gene. The T allele of this SNP has been associated with an increased risk of bevacizumab-induced hypertension.

AlleleImplications
TIncreased risk of bevacizumab-induced hypertension
CNormal risk of bevacizumab-induced hypertension

rs10051982 is an SNP in the SV2C gene. The A allele of this SNP has been associated with an increased risk of bevacizumab-induced hypertension.

AlleleImplications
AIncreased risk of bevacizumab-induced hypertension
GNormal risk of bevacizumab-induced hypertension

Non-genetic Factors Influencing Hypertension During Chemotherapy

Bevacizumab Dosage

The effect of bevacizumab is dose-dependent. People who were treated with a higher dose of the medication (>10 mg/kg) had a 7.5-times higher risk for developing hypertension. 

Age

People aged 60 and above have a higher risk of developing bevacizumab-induced hypertension when treated for cancer.

BMI Levels

People with BMI levels of 25 and above have a higher risk of developing bevacizumab-induced hypertension.

Pre Existing  Hypertension 

Those who have had high blood pressure before bevacizumab treatment are at a higher risk for developing high-grade bevacizumab-induced hypertension.

Type of Cancer

Among cancer patients who receive Bevacizumab, the risk of developing hypertension depends on the type of cancer. People with breast cancer or renal cell carcinoma show the highest risks for bevacizumab-induced hypertension.

Presence of other diseases

People with below pre-existing health conditions before bevacizumab treatment are at higher risk of developing hypertension during the treatment.

Tips To Prevent/Manage Hypertension Due To Chemotherapy (In Breast Cancer)

Talk To Your Doctor To Get The Right Information

If your doctor suggests bevacizumab medication along with chemotherapy, then talk to your doctor to understand the risks associated with the drug. Understand how effective it could be to treat your breast cancer and if the benefits outweigh the risks. 

Closely Monitor Your Blood Pressure Levels

The blood pressure starts rising from the first cycle of bevacizumab treatment. Make sure you closely monitor your levels at home and in a professional setup regularly. Talk to your doctor and opt for hypertension medications to prevent making the condition worse.

Manage Existing Hypertension Before Getting Treated For Breast Cancer

If you are already diagnosed with hypertension, make sure to stabilize your blood pressure levels  before starting cancer therapy. 

Start Antihypertensive Medications And Make Lifestyle Changes

Antihypertensive drugs help bring down blood pressure levels. It is recommended that you start on these along with your cancer treatment to prevent the risk of bevacizumab-induced hypertension. Make sure to consult a medical practitioner before getting started on any antihypertensives.

Some lifestyle changes can also help manage the condition.

Opt For Genetic Testing

Genetic testing before opting for bevacizumab will tell you how risky you are for developing hypertension during cancer treatment. If you are a high-risk patient, mention this to your doctor so they can monitor your blood pressure levels more frequently. 

Summary

  1. Bevacizumab is a medication used in the treatment of certain types of cancers. It is used along with chemotherapy to stop the growth of tumor cells.
  2. Though the FDA has currently removed bevacizumab from the list of approved medicines to treat breast cancer, doctors can still use it with the patient’s approval.
  3. Bevacizumab causes many side effects in cancer patients, including hypertension.
  4. Changes in some genes like the  SV2C gene can increase the risk of developing bevacizumab-induced hypertension.
  5. The risk of developing hypertension increases with higher doses of bevacizumab. People aged 60 and above and those with BMI levels about 25 are at higher risk too.
  6. The prevalence of other diseases like diabetes mellitus, high cholesterol, kidney problems, and peripheral artery disease also increases the risk of bevacizumab-induced hypertension.
  7. Antihypertensive medications can help bring down the risk of high-grade hypertension. People undergoing bevacizumab therapy should regularly monitor blood pressure levels. 

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References

Just like how water exerts pressure on the walls of the pipes when flowing, blood too exerts pressure on the surface blood vessels.

The pressure exerted must be constant and of a particular value. A drop or hike in this pressure may likely be a warning of an abnormality.

When the pressure exerted by blood on the walls increases beyond a certain level, it is known as hypertension or high blood pressure.

Hypertension is a common health condition. Nearly half the American population is expected to be diagnosed with hypertension. 

Symptoms Of Hypertension

Most people don’t experience any particular symptom until the condition becomes severe. That is why hypertension is rightly known as the "silent killer”. Even when people do experience the symptoms, they are almost always associated with other issues.

What Are The Symptoms Of Hypertension?

What Causes Hypertension?

The causes of hypertension or high blood pressure are still being studied. Some of the well-accepted and scientifically proven causes are smoking, obesity or being overweight, diabetes, having a sedentary lifestyle (one involving very minimal physical activities), and unhealthy eating habits. 

When it comes to diet, a high salt intake can result in hypertension, especially if you are 'salt-sensitive.'

What Is Salt Sensitivity?

We all require some amount of salt in our diets to survive. As its chemical name sodium chloride suggests, salt contains an important mineral, sodium.

Salt sensitivity is a measure of how your blood pressure responds to salt intake. People are either salt-resistant - their blood pressure doesn't change much with salt intake or salt-sensitive - their blood pressure increases upon salt consumption.

About 60% of people with high blood pressure are thought to be salt-sensitive.

How To Determine If You Are Salt Sensitive?

If you suspect salt sensitivity, the best way forward is to approach your medical practitioner. 

Your practitioner may initially put you on a low sodium diet. This can then be switched to a high sodium diet. 

If there's a rise in the blood pressure by 5-10% after the switch, then you may be considered salt sensitive.

The Story Behind Salt Sensitivity

When our ancestors were roaming about in Africa, many thousands of years ago, salt may have been a scarce nutrient in their diets.

Our bodies require salt for a lot of important functions like muscle contraction, maintaining blood volume, and sending messages and signals between the cells.

Salt also plays a role in water retention in the body. In archaic times when our ancestors were out and about in the Savannah, exposed to the sun for long periods of time, being salt-sensitive would have given them an advantage by losing less water to the environment. 

Salt retention became even more essential when infectious diseases (which often cause people to lose sodium through diarrhea and vomiting) started to spread.

Researchers speculate that this is the reason why humans probably developed the sensitivity to salt. 

So, an ability to hold on to this nutrient was a survival advantage in many ways. 

Unfortunately for many of us, we have retained this evolutionary ability to hold on to calories and sodium ever so dearly. Being surrounded by an environment filled with high-salt and high-calorie foods has automatically ended up increasing our risk of obesity and hypertension. 

Surprisingly, salt is not only found in salty foods, but many sweet-tasting foods have large amounts of salt in them. Salt is used as a taste enhancer and a preservative.

Many brands that make cake and pastries hide some amount of salt in them in order to enhance the taste. 

ACE Gene, Salt (Sodium), And Blood Pressure Control - Molecular aspect

The kidneys control blood pressure by either excreting or reabsorbing sodium. Since sodium moves with water, it is excreted as urine when the blood pressure needs to be lowered. By contrast, the kidneys reabsorb sodium in order to increase the blood pressure.

Our blood pressure is also regulated by the widening and narrowing of the blood vessels to regulate the blood flow.

The ACE gene produces the angiotensin-converting enzyme and plays a key role in controlling blood pressure.  

Whenever there's a drop in the blood pressure, it triggers the release of a hormone, renin, from the kidneys. Renin helps form a molecule, angiotensin 1. Angiotensin 1 and 2 are two forms of the hormone angiotensin, that controls the narrowing of the blood vessels to regulate blood pressure. Angiotensin-converting enzyme or ACE, released by the lungs, converts angiotensin 1 to angiotensin 2. Angiotensin 2 triggers the release of another hormone, aldosterone, that helps kidneys reabsorb sodium and water, thereby increasing the blood pressure.

The Genetics Behind Salt Sensitivity and Blood Pressure

Some types of ACE gene increase the production of the angiotensin-converting enzyme. This results in an increased sodium absorption, thereby causing a higher than normal spike in the blood pressure. 

rs4343

The SNP rs4343 influences the production of the angiotensin-converting enzyme in response to sodium (salt) in blood. The A allele of rs4343 has been associated with increased blood pressure on high salt intake.

Food recommendations for salt-sensitivity

People who are salt sensitive should watch the sodium content in their diet. Foods that are low in sodium and high in potassium are recommended - potassium lessens the effect of sodium.

The DASH diet is popular among people with high blood pressure. This diet emphasizes fruits and vegetables - both of which are low in sodium and high in potassium. It also includes nuts, whole grains, poultry, and fish. 

Dairy products also are a good addition to the diet. Milk, yogurt, cheese, and other dairy products are major sources of calcium, vitamin D, and protein.

Other low sodium foods include basil, apples, cinnamon, brown rice, kidney beans, and pecans.

Summary

While retaining salt in the body was a survival advantage for our ancestors, the same has become a villain in this day and age of high-calorie and high-salt foods all around. Hypertension, characterized by a persistent elevation in the blood pressure, is a risk factor for many serious conditions like heart disease and stroke. Depending on our sensitivity to the sodium in salt, our blood pressure either spikes or lurks in the normal range upon consumption of salt. The ACE gene plays an important role in determining our sensitivity to salt. The ‘salt-sensitive’ individuals must be wary of the amount of sodium (salt) intake in order to maintain their blood pressure in the normal range. The DASH diet is popular among people who are trying to limit their salt intake.

References

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214830/
  2. https://pubmed.ncbi.nlm.nih.gov/11711524/
  3. https://en.wikipedia.org/wiki/Angiotensin
  4. https://www.healthline.com/nutrition/dash-diet

25% to 50% of people who reported to hospitals in China with coronavirus in December 2019, had hypertension or other comorbidities like diabetes, cancer, or heart conditions. In Italy, 75% of COVID-related deaths included hypertensives. Hypertension and severe COVID symptoms have a genetic connection. But how interlinked are they? Read on to find out more!

Introduction

The clinical and epidemiological features of COVID-19 have been under constant study and several research studies have been published about it over the last several weeks.

A lot of focus is on the comorbidities that have an association with COVID, in particular.

The most common comorbidities in one report were hypertension (30%), diabetes (19%), and coronary heart disease (8%).

ACE inhibitors, which are used to treat hypertension, have been researched to increase the ACE2 receptor expression, to which the coronavirus binds to.

But, it is important to note that none of these can be declared as a 'cause' of COVID since these are more prevalent in the elders, who appear to be at an increased risk for COVID.

However, blood pressure control is extremely important to reduce the impact of COVID in your body.

Genetics and COVID

The coronavirus appears to affect any individual despite factors like their age or gender.

However, recent research reveals that some people tend to have more severe symptoms, in comparison to others who may experience mild symptoms or be completely asymptomatic.

Some genetic factors tend to influence how the virus enters your body, and consequently, how the virus affects you as well.

Hypertension - A risk factor for COVID?

There is a wide acceptance amongst the scientific community that there is a genetic risk factor that causes severe symptoms in some individuals, while rendering other asymptomatic.

One such disease that scientists have researched is hypertension.

The limited studies on this reveal that the novel coronavirus latches on to the human protein ACE2 receptors and gains entry into the lungs. 

Hypertensive individuals are prescribed Angiotensin-Converting Enzyme(ACE) inhibitors, and some studies have shown that these medications increase the number of ACE receptors, thereby increasing the portals for entry of the virus.

There are, however, opposing theories with a few groups of scientists saying that the ACE2 can actually protect the lungs from a very severe infection of 2019- nCov.

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Diabetes: A Common Comorbidity of COVID-19: Check Your Risk With 23andMe Raw Data

Genetics’ play in hypertension

A very common health condition that is prevalent today is hypertension or abnormally high blood pressure.

A blood pressure level of 120/80mm Hg is considered normal, and having blood pressure equal to or higher than 130/80 mm Hg is called hypertension, in an otherwise healthy individual. 

Though a common condition today, hypertension runs in families, and therefore, genetics and heredity may play a major role in determining the disease risk.

Individuals who have hypertensive parents tend to have an increased risk of developing the condition. However, how the exact inheritance of this condition is still unknown.

Many Genome-Wide studies have been conducted to study the influence of genes on the development of hypertension. 

Around 280 genetic variants have been found that are said to increase the risk of hypertension and other associated conditions such as coronary artery disease.

Hypertension and COVID: Reducing your risk using 23andMe DNA data

Some genes that have a significant role to play in the development of hypertension are –

With the currently available studies, it has been observed that there are many genes that play a role in the pathophysiology of hypertension. It is highly unlikely that just one or two will emerge as the leading genes associated with the condition.

Now it is as simple as just following 3 simple steps to identify your risk for hypertension using your DNA raw data.

Signs to look out for to check for COVID when you have hypertension

So far, it is quite evident that hypertension is high-risk comorbidity that results in severe symptoms if affected by COVID.

Pneumonia is one of the most common complications in severe cases.

In a hypertensive individual, high blood pressure damages the blood vessels and arteries. Therefore, it results in reduced blood flow to the heart.

As a result, your heart needs to work extra hard to pump blood, so it reaches all parts of your body.

When this happens over a period of time, it results in the weakening of the heart muscles.

The same effect can occur when there is hypercholesterinemia occurs together with hypertension.

Most common symptoms to look out for if you suspect a COVID infection include:

Tips for managing your blood pressure to reduce your risk for COVID

As a hypertensive individual, you need to take extra care to reduce your chances of contracting COVID. Here are some guidelines that you need to follow:

References

https://www.cebm.net/covid-19/coronaviruses-a-general-introduction/

https://academic.oup.com/eurheartj/article/38/29/2309/3852720

https://jasn.asnjournals.org/content/13/suppl_3/S155

https://academic.oup.com/ajh/article/33/5/373/5816609

https://pubmed.ncbi.nlm.nih.gov/24842388/

Do you have your DNA raw data file from 23andMe, AncestryDNA, FTDNA, LivingDNA, etc.?

Upload your DNA raw data to Xcode Life to know your genetic predisposition to hypertension.

Published on 29, June 2020

What does the CYP1A2 gene do? 

CYP1A2 codes for the production of 21-hydroxylase, which is part of the cytochrome P450 family of enzymes.

This family of enzymes is quite important as it is a part of many processes, that include breaking down drugs, production of cholesterol, hormones, and fats.

The adrenal glands secrete the enzyme, 21-hydroxylase.

Situated on the top of the kidneys, the adrenal glands also produce hormones like epinephrine and cortisol.

Incidentally, 21-hydroxylase plays a role in the production of cortisol and another hormone named aldosterone.

Cortisol is a stress-related hormone and plays a role in protecting the body from stress, as well as reducing inflammation.

Cortisol also helps in maintaining blood sugar levels.

Aldosterone, also known as the salt-retaining hormone, regulates the amount of salt retained in the kidneys.

This has a direct consequence on blood pressure, as well as fluid retention in the body. 

There seems to be an interesting trend in the activity of the CYP1A2 gene and caffeine intake.

The consequence of being a “rapid” or a “slow” metabolizer of caffeine can have effects on an individual’s cardiovascular health.

This article explains the wide-ranging effects of this gene, caffeine intake,  cardiovascular health, hypertension, and even pregnancy!

What is the association between CYP1A2 and caffeine metabolism?

In the body, CYP1A2 accounts for around 95% of caffeine metabolism.

The enzyme efficiency varies between individuals.

A homozygous, that is, AA genotype represents individuals that can rapidly metabolize caffeine.

Some individuals have a mutation in this locus and thus have the AC genotype.

These individuals are “slow” caffeine metabolizers.

CYP1A2 and cardiovascular health

There seems to be a link between CYP1A2, the incidence of myocardial infarction (MI), and coffee intake.

The positive effects of coffee include lowering a feeling of tiredness and increasing alertness; however, it can also narrow the blood vessels.

This increases blood pressure and could lead to cardiovascular disease risk.

Rapid metabolizers of coffee have the AA genotype and may unravel the protective effects of caffeine in the system.

However, the individuals that are slow metabolizers have a higher risk of MI.

This suggests that the intake of caffeine has some role in this association. 

Yet another study associated DNA damage due to mutagens found in tobacco smoking could contribute to MI.

The study included participants who were genotyped at the CYP1A2 gene.

They found a group of ‘highly inducible’ subjects that had a CYP1A2*1A/*1A genotype.

These individuals have a greater risk for MI, independent of their smoking status.

This also means that there is some intermediary substrate that the CYP1A2 gene decomposes, and if this gene has a mutation, it could lead to a higher risk of MI. 

In a study conducted on 2014 people, people who were slow metabolizers of caffeine (C variant) and who consumed more than 3 cups of coffee per day had an association with increased risk for myocardial infarction. 

In a similar study on 513 people, increased intake of coffee, among slow metabolizers, has an association with an increased risk for hypertension.

The association between smoking and hypertension

Smoking is capable of inducing the CYP1A2 enzyme. Smokers exhibit increased activity of this enzyme.

In a study conducted on 16719 people, people with the A variant, and who were non-smokers, were 35% less likely to be hypertensive than people with the C variant.

In the same study, CYP1A2 activity had a negative association with blood pressure among ex-smokers.

But for people who were still smoking, the same gene expressed an association with increased blood pressure.

The gene CYP1A2 also has an association with caffeine metabolism and smoking.

A study aimed to tie these concepts together to find the relationship between this gene and blood pressure (BP).

The main measurements of the study were caffeine intake, BP, and the activity of the CYP1A2 gene.

In non-smokers, CYP1A2 variants (having either a CC, AC, or AA genotype) were associated with hypertension.

Higher CYP1A2 activity was associated with people who quit smoking and had lower BP compared to the rest but had a higher BP while smoking.

In non-smokers, CYP1A2 variants (having either a CC, AC or AA genotype) were associated with high caffeine intake, and also had low BP.

This means that caffeine intake plays some role in protecting non-smokers from hypertension, by inducing CYP1A2.

The effect of the CYP1A2 on pregnancy and caffeine intake

The intake of caffeine during pregnancy has an association with the risk of reduced fetal growth.

High caffeine intake shows a link to decreased birth weight.

The babies are also at risk of being too small during the time of pregnancy.

This was also observed in a study conducted on 415 Japanese women.

Women with the A variant who drank more than 300 mg of coffee per day were shown to be at an increased risk of giving birth to babies with low birth weight.

Summary

In conclusion, there are a lot of effects that the CYP1A2 gene has on the body. Many studies, as noted above, seem to link the activity of this gene to caffeine intake.

A variant at the CYP1A2 gene can determine whether an individual is a fast or slow metabolizer of caffeine, and this has some effect on the blood pressure and cardiovascular health of an individual.

The gene also plays a role in regulating an infant’s weight during the pregnancy of a woman,  and this has a link with caffeine intake. It is thus interesting to analyze the effect of the variants of the CYP1A2 gene on an individual, based on their caffeine intake. 

References

  1. https://ghr.nlm.nih.gov/gene/CYP21A2
  2. https://jamanetwork.com/journals/jama/fullarticle/202502
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474926/
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1735605/
  5. https://www.researchgate.net/publication/223974368_Caffeine_intake_and_CYP1A2_variants_associated_with_high_caffeine_intake_protect_non-smokers_from_hypertension
  6. https://www.nature.com/articles/pr201770#:~:text=Maternal%20caffeine%20intake%20may%20increase,8%2C%209%2C%2010)

Do you have your DNA raw data from 23andMe, AncestryDNA, FTDNA, LivingDNA, etc.?

Upload it to Xcode Life to know about your CYP1A2 caffeine metabolism and caffeine sensitivity variants.

Published on 18 June, 2020

Caffeine acts as a stimulant of the Central Nervous System (CNS), causing increased alertness.

It is the world's most widely consumed legal psychoactive drug.

Caffeine offers a range of benefits from something as small as over an afternoon slump to reducing the risk of some serious health conditions like heart diseases.

Some common food sources of caffeine include:

How does caffeine affect your body?

Up to 400 milligrams of caffeine appears to be safe for most healthy adults.

Anything exceeding that can be harmful to the body.

The effect of caffeine on various systems of the body are as follows:

Central Nervous System (CNS)

Caffeine is a stimulant and causes mental alertness once it reaches the brain.

It is a common ingredient in medications that are meant to treat drowsiness, migraines, and headaches.

Digestive and excretory systems

Caffeine stimulates the production of stomach acid and can cause heartburn, acid reflux, or stomach upset.

Excess caffeine is stored in the liver, which exits through urine.

Hence, drinking excessive coffee or tea increases the urge for urination.

Respiratory and circulatory systems

Caffeine intake increases adrenaline production.

This, in turn, increases your blood pressure for some time.

When consumed in excess quantities, caffeine can lead to irregular heartbeat and breathing.

Skeletal system

Excess caffeine interferes with the absorption and utilization of calcium.

Reduced calcium levels in the body can lead to osteoporosis.

Muscular system

Muscle twitching is often a visible symptom of excess caffeine consumption.

Reproductive system

A little caffeine during pregnancy appears to be safe in most cases.

However, it is important to note that caffeine can cross the placental barrier, and therefore, can affect the fetus.

It can increase the fetus's heart rate and, in some cases, may even lead to a miscarriage.

CYP1A2: How does this gene affect caffeine consumption?

CYP1A2 codes for a protein that belongs to the Cytochrome P450 family.

This protein is involved in the breakdown of stimulants, drugs, nutrients, and other xenobiotics.

The CYP1A2 gene regulates the synthesis of the enzyme, and small variations in this gene are associated with the efficiency of caffeine metabolism.

Some people are genetically predisposed to produce very little of CYP1A2 enzyme while others may generate a sufficient amount.

Approximately 10% of the population is found to be rapid caffeine metabolizers, showing a high tolerance to caffeine.

This enzyme is also essential for removing toxic chemicals from our body and processing hormones and other products of metabolism.

Both increased and decreased enzyme activity have been linked to an increased risk of cancer.

It is a significant protein family in the human body, as it majorly decides how an individual responds to drugs and nutrients.

Variations in this gene broadly divide people into two groups of metabolizers:

CYP1A2: Gene polymorphism:

In particular, two Single Nucleotide Polymorphisms (SNP) are found to influence caffeine metabolism:

rs762551

The haplotype CYP1A2*1F is associated with this variation.

[table id=100 /]

rs2472297

Individuals who have the TT genotype in this specific polymorphism of the CYP1A2 gene may be fast metabolizers of caffeine.

study conducted on 553 individuals found that people with this genotype had a 70% reduction in the risk of a heart attack on increased consumption of caffeine.

[table id=101 /]

Why should you know your genetic predisposition to consume caffeine?

People of certain genetic types have a genetic predisposition to drink more cups of coffee.

Identification of this tendency will help in moderating coffee consumption, taking into account the individual's caffeine metabolism status.

Genetic tests can help identify such parameters.

After all, it would be good to know if you are prone to guzzling down a little too much, especially when your caffeine sensitivity scale is tipped at the wrong end.

CYP1A2: Caffeine tolerance

Caffeine tolerance in an individual is gene deep.

The enzyme CYP1A2 is responsible for metabolizing caffeine in the body and determines whether the individual is a slow or a fast caffeine metabolizer.

Fast metabolizers of caffeine may have a high caffeine tolerance.

Such people have two copies of the fast variant.

Some people have one slow and one fast copy of the variant and are said to be moderately tolerant to caffeine.

However, those individuals who have two copies of the slow variant are slow metabolizers of caffeine and are said to be poorly tolerant of it.

How does caffeine affect your metabolism?

Resting metabolic rate describes the rate at which you burn calories at rest.

A lot of studies vouch for caffeine boosting the RMR. 

Early research also suggests that caffeine supports fat-burning during exercise.

This increase in fat-burn is what majorly contributes to the increase in metabolism.

Initially, the increase in metabolism upon caffeine consumption can be evident. 

However, this effect can diminish in long-term coffee drinkers due to the developed tolerance.

If you're primarily interested in coffee for the sake of fat loss, it may be wise not to consume it excessively and end up making your body more tolerant of caffeine.

Effects of excessive caffeine intake

Caffeine is a component in many plants, including coffee and tea.

The primary purpose of it is to act as a toxin to defend the plants against herbivores.

Caffeine in limited quantities is beneficial to our health, but in excessive amounts, harmful.

The effects of excessive caffeine intake (more than 4-5 cups of strong tea or coffee) include:

  1. Tremors
  2. Increased urination
  3. Increased heart rate
  4. Nervousness
  5. Stomach upset
  6. Anxiety
  7. Increased blood pressure
  8. It can cause restlessness in unborn babies and hyperactivity in kids

How do you remove caffeine from your body?

Excessive caffeine consumption does come with a set of undesirable effects.

During such times, the following remedies can help flush out caffeine from the system:

If nothing else works, just wait! The half-life of caffeine in the human body is roughly 4-6 hours, which means caffeine naturally starts to breakdown after that time. 

What is caffeine withdrawal?

If your body is dependent on caffeine, eliminating caffeine from your diet may cause symptoms of withdrawal.

This occurs typically 12-24 hours after stopping caffeine.

The symptoms of caffeine withdrawal are:

Ways to reduce caffeine withdrawal symptoms:

References:

  1. https://www.ncbi.nlm.nih.gov/gene/1544
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3346273/

Do you have your DNA raw data from 23andMe, AncestryDNA, FTDNA, MyHeritage?

Upload your DNA raw data to Xcode Life. Our Gene Nutrition Report analyses caffeine sensitivity and metabolism, gluten sensitivity, lactose intolerance, vitamin needs, and 33 more such categories.

Updated on 09 June, 2020

What is type II diabetes?

Diabetes mellitus type II is a long term metabolic disorder that results in high blood sugar, insulin resistance, and/or lower insulin levels.

According to the American Diabetes Association, 9.3% of the US population has this disorder. 

Formerly known as adult-onset diabetes, it occurs most often in middle-aged and older people. 

Over time, high blood glucose can cause serious complications with the heart, eyes, kidneys, nerves, gums, and teeth. 

What causes type II diabetes?

The special cells in the pancreas, called the beta cells produce a hormone called insulin. 

Insulin moves blood sugar or glucose into the cells. 

In type 2 diabetes, the fat, liver, and muscle cells respond incorrectly to insulin. 

This is called insulin resistance. 

The glucose is incapable of entering the cells, and a high level of sugar builds up in the blood. 

This is known as hyperglycemia. 

Insulin resistance is the most common cause of type 2 diabetes.

But sometimes, type 2 diabetes can be caused by decreased production of insulin by the beta cells.

What are the symptoms of type 2 diabetes?

Type 2 diabetes can cause serious complications, so it is essential to identify the symptoms as early as possible.

Most of the symptoms are a result of increased blood sugar levels. These include:

  1. Increased thirst
  2. Increased hunger
  3. Frequent urination
  4. Fatigue
  5. Dry mouth
  6. Unexplained weight loss
  7. Blurred vision
  8. Headache

Other symptoms of type 2 diabetes include:

  1. Slow-healing sores or cuts
  2. Velvety dark skin changes of the neck, armpit, groin
  3. Numbness and tingling of hands and feet
  4. Decreased vision

What are the type 2 diabetes risk factors?

Chances of developing type 2 diabetes depend on a combination of risk factors, including genes and lifestyle.

While the genetic risk factors cannot be changed, making the required changes in our lifestyle is very much within our hands. 

You are more likely to develop type 2 diabetes if you

Hand-Picked article for you: Have Your 23andMe Raw Data? Use It To Get 500+ Health-Related Genetic Traits!

The genetic component to type II diabetes

Research has identified at least 150 genetic variations associated with the risk of developing type 2 diabetes. 

Each person possesses variations that can either increase or decrease the risk. 

The combination of these variations determines a person's likelihood of developing the disease. 

The genetic variations may directly or indirectly affect the following:

However, for many of the variations associated with type 2 diabetes, the mechanism by which they contribute to the disease is unknown

Gene 1: IGF2BP2

IGF2BP2 gene encodes a protein that binds the 5’ UTR of insulin-like growth factor 2 mRNA and regulates its translation.

It plays an important role in metabolism, and variation in this gene is associated with susceptibility to diabetes.

Studies have shown an increased risk of T2D for those with the rs4402960 polymorphism.

In the case-control study, the carriers of TT genotype at rs4402960 had a higher T2DM risk than the G carriers (TG + GG)

rs4402960

[table id=90 /]

In conclusion, the analysis suggested that rs4402960 polymorphism in IGF2BP2 is associated with elevated T2D risk, but these associations vary in different ethnic populations. 

Gene 2: PPARG

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays a critical role in regulating insulin sensitivity and glucose homeostasis and can be associated with improved insulin sensitivity.

Research has shown that PPAR-γ directly activates GLUT2 and β-glucokinase (important to glucose homeostasis)

Additionally, PPAR-gamma has been implicated in the pathology of numerous diseases, including obesity, diabetes, atherosclerosis, and cancer.

Inactivating mutations of the gene encoding PPAR gamma are associated with insulin resistance type 2 diabetes.

rs17036314 is an SNP in the PPARG gene found to increase the chance of type 2 diabetes.

rs17036314

[table id=91 /]

Gene 3: SLC30A8

SLC30A8, a zinc transporter gene, is associated with type 2 diabetes.

It is involved in the accumulation of zinc in intracellular vesicles.

This gene is expressed at a high level only in the pancreas, particularly in the islets of Langerhans.

The common polymorphism rs13266634 was associated with lowered beta-cell function and a 14% increase in diabetes abundance per risk (C) allele.

This variant encodes a tryptophan-to-arginine switch at position 325 in the protein.

This results in reduced zinc transport activity and, consequently, decreased intragranular zinc levels. 

The SLC30A8 polymorphism is found associated with reduced insulin secretion, but not with insulin resistance.

rs13266634

[table id=92 /]

Gene 4: HHEX

HHEX gene encodes a member of the homeobox family of transcription factors. Its polymorphisms show association with type 2 diabetes.

The major role of HHEX protein is interacting with signaling molecules.

It plays a role in embryonic development of the pancreas, liver, and thyroid.

A study linked that polymorphism rs7923837 is associated with impaired insulin response.

The risk allele of rs1111875 and rs7923837 in the HHEX gene are associated with reduced beta-cell secretion capacity.

rs1111875

[table id=93 /]

rs7923837

[table id=94 /]

Gene 5: TCF7L2

The TCF7L2 gene plays a role in controlling blood sugar levels.

It is involved in adipogenesis (formation of fat cells) and is associated with glucose intolerance and impaired insulin secretion.

The SNP within the TCF7L2 gene, rs7903146, plays a role in this association.

The risk allele results in the overexpression of the gene in the pancreatic beta cells, thus reducing insulin secretion.

The reduced insulin secretion explains the increased hepatic glucose production. 

In conclusion, the increased risk of T2D conferred by variants in TCF7L2 involves the enhanced expression of the gene in islets and impaired insulin secretion.

rs7903146

[table id=95 /]

Gene 6: KCNJ11

KCNJ11, in tandem with several other genes, mediates the regulation of insulin released.

Reduced expression of KCNJ11 may increase the risk of type II diabetes.

The rs5219 A allele plays a crucial role in insulin secretion by decreasing the ATP sensitivity of the Potassium ATP channel and suppressing insulin secretion. However, the mechanism involved is still unclear. 

rs5219

[table id=96 /]

You may also be interested in Diabetes: A Genetic Overview

What do I do with my genetic information?

Type II Diabetes is a complex condition with several contributing factors, genetics included.

Certain genetic predispositions increase the individual's risk of developing the disorder; however, it is not a guarantee that the person will go on to develop that condition.

This is because other factors play a role in its onset.

Knowing your genetic makeup empowers you with information to reduce the risk of developing type II diabetes by altering the factors that are in your control.

How to prevent the onset of type II diabetes?

Research such as the Diabetes Prevention Program shows that you can do a lot to reduce your chances of developing type 2 diabetes. Here are some things you can change to lower your risk:

You may be able to prevent or delay diabetes by losing 5 to 10 percent of your current weight.

For example, if you weigh 250 pounds, your goal would be to lose between 12.5 to 25 pounds.

Insulin resistance reduces with regular exercises and better utilization of glucose by the cells. 

Choose foods that have lesser fat content.

If losing weight is the goal, a high-fiber, low-fat diet may help you.

Drink water in plenty and stay away from those soft drinks!

Hand-picked content for you: Drinking 2 or more sugary drinks per day doubles diabetes risk

Diabetes-friendly diet:

Altering one's diet is one of the best ways to prevent type 2 diabetes, and this can be done by including and excluding a few items in the diet.

Foods to eat:

A diet of beans, vegetables, nuts, seeds, and fresh fruit can prevent type II diabetes.

High nutrient, low glycemic load foods are the best food for diabetics and those looking to prevent it.

An analysis found that leafy vegetable intake was related to a 14% decrease in the risk of type 2 diabetes.

They have close to no effect on blood glucose and are rich in fiber and phytochemicals.

Beans have low glycemic load due to their increased fiber and resistant starch (carbohydrates that are not broken down in the small intestine).

Eating three servings of fresh fruit each day results in an 18% decrease in the risk of diabetes.

Foods to Avoid:

Foods that increase blood sugar levels or reduce sensitivity to insulin increase the risk for type 2 diabetes. These include:

Fibers slow down the absorption of glucose into the blood.

However, these foods are devoid of sugar and can cause a sharp increase in blood glucose levels.

They increase the chances of getting type 2 diabetes in the long run.

This leads to increased glucose levels and a greater risk of diabetes.

A meta-analysis conducted concluded that:

You can use your 23andMe DNA raw data to learn about your type 2 diabetes risk

Xcode Life Gene Health Report analyzes the genetic variants for type 2 diabetes, anxiety, heart disease, and more than 45 categories of health-related traits.

Our affinity for alcohol is not new; in fact, we developed it ten million years ago, even before we evolved into humans! The natural source of alcohol is fruits, with usually less than 1% of ethanol in ripe fruits and up to 8% in overripe fruits. The presence of alcohol was beneficial both for our primate ancestors as well as the plants that bore the fruits. The strong smell of alcohol traveled far and wide, attracting primates. This helped primates reach food sources while they helped the plants by dispersing the seeds. Alcohol was considered highly beneficial when fruits were its major source. In the present time, where alcoholic drinks are available in large quantities and are consumed in higher concentrations, they tend to do more harm than good.

Alcohol flush reaction: What is it?

The consumption of alcohol in some individuals causes blotches of erythema on their face and neck region, and sometimes on the entire body. Such an event is called an alcohol flush reaction.

Most of the time, it happens as a result of improper digestion of alcohol.

Accumulation of acetaldehyde in the body after alcohol consumption leads to this reaction.

When you consume alcohol, it gets metabolized to its byproduct acetaldehyde.

In typical cases, acetaldehyde gets metabolized further.

An enzyme called aldehyde dehydrogenase, coded by the gene ALDH2, is responsible for this metabolism.

However, some individuals have a defective gene that prevents the further metabolism of acetaldehyde.

This causes its accumulation in the body resulting in an alcohol flush reaction.

More about the enzyme

There are two types of enzymes responsible for the breakdown of alcohol: alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. Acetate is synthesized with the help of aldehyde dehydrogenases (ALDH), mostly by ALDH2, a mitochondrial enzyme, but also by ALDH1, the cytosolic enzyme. 

There are five different types of ADH enzymes based on structural similarity and kinetic properties. 

Class I enzymes: The class I enzymes are coded by the ADH1A, ADH1B, and ADH1C genes, which are associated with about 70% of the total ethanol oxidizing capacity.

II: The class II enzymes are coded by the ADH4 gene, which is associated with about 30% ethanol oxidizing capacity. 

III: The class III enzymes are coded by the ADH5 gene and is the only class of enzyme that is detected in the brain. 

IV: The class IV enzymes are coded by the ADH7 gene and are found mainly in the upper digestive tract, where it oxidizes ethanol at high concentrations. 

V: The class V enzymes coded ADH6 gene are found in a variety of substrates, including retinol but are less efficient in ethanol metabolism.

Who is more prone to alcohol flush?

People of Asian descent, especially the East Asian descent, are more susceptible to have an alcohol flush reaction.

In fact, this red face phenomenon is also called the "Asian flush or "Asian glow."

According to some studies, over 70% of East Asians have genetic polymorphisms in either ADH or ALDH2, leading to intense flushing with ethanol consumption.

What happens during an alcohol flush reaction?

Other than the primary flushing red face, the other symptoms include:

Is the reaction dangerous?

While the flushing by itself may not to be dangerous, the reaction may have other health-related implications.

A 2013 study reported that people who experience an alcohol flush reaction on drinking might have a higher chance of developing hypertension, or high blood pressure.

Another study done on East Asian men in 2017 found an association between high risk of cancer, especially esophageal cancer, and flushing reaction.

This can be due to the high levels of acetaldehyde, which can trigger the growth of cancer cells.

How's it diagnosed?

When you report with suspected alcohol flush reaction, your doctor may first perform a physical examination. Other confirmatory tests also help with the diagnosis.

Skin test 

It detects your allergy, if any, to a substance in alcoholic beverages such as grains like maize, rye, and wheat. 

A little amount of the substance is injected into your skin, and the reaction is studied. If the skin appears red and raised, you are noted positive for the test.

Blood test

A blood test is done to detect the presence of antibodies like IgE that are found in the blood when there is an allergic reaction to a substance in alcohol.

Enzyme test

Measuring the amount of alcohol metabolizing enzymes, alcohol dehydrogenase and aldehyde dehydrogenase, can predict the intensity of reaction that one may experience.

Genetic test

The gene responsible for acetaldehyde metabolism in the body is ALDH2 that produces the enzyme ALDH2 or Aldehyde Dehydrogenase 2. 

Individuals who suffer from an alcohol flush reaction may have a faulty or deficient ALDH2 gene, and this can be identified using genetic testing.

Treating alcohol flush reaction

There is no definitive treatment for the root cause of this reaction, ALDH2 deficiency.

However, there are options when it comes to managing the symptoms.

  1. Antihistamines or histamine blockers can help control facial flushing.
  2. Another treatment, brimonidine, approved by the FDA for treating rosacea (a skin condition that causes redness in your face), can be effective for managing the flushing as well.
  3. Some laser-based therapies are also helpful to control the redness in the face.

Alcohol flush prevention

The only foolproof way to prevent this reaction is to avoid or limit your alcohol intake.

A lot of people tend to use OTC antihistamines to manage the reaction, but this is strongly not advisable.

The first and foremost step is to recognize your risk for this condition by studying your ALDH2 gene variants.

Check your 23andMe raw data or your Ancestry DNA raw data to find out the variant you carry

[table id=77 responsive=scroll/]

According to the variant you carry, you might need to limit or discontinue alcohol consumption.

Other unwanted reactions to alcohol consumption addressed

Why do I bleed after a night of drinking?

Alcohol irritates the gastric lining.

When you drink alcohol, even a small quantity of it, it causes your stomach to produce acid.

Consumption of excess alcohol leads to increased production of stomach acid, which can lead to gastritis.

In many cases, due to excess alcohol, it triggers pain in the stomach, causes diarrhea, vomiting, and even bleeding.

Why do my ears burn when I drink alcohol?

Alcohol affects almost all parts of our body.

Consumption of excess alcohol affects the part of the brain that controls hearing.

In fact, alcohol consumption affects ears and hearing in more than one way.

When we drink alcohol, it also gets absorbed in the fluid of our ears and causes a burning sensation.

Does alcohol cause hot flashes?

Alcohol causes hot flashes in women, especially those going through menopause.

Does alcohol increase body temperature?

Having even a few sips of alcohol can make you feel warmer.

This is because alcohol makes the blood vessels underneath your skin dilate and increases the blood flow in them, which can induce the 'warm feeling.'

But in reality, alcohol reduces your core temperature.

What are some steps to reduce alcohol consumption?

Reducing alcohol consumption can immensely improve your health. Here is a list of a few things you can do to help you reduce drinking:

  1. Keep track of your drinking habits, and change them if warranted
  2. Drink slowly and hydrate yourself with water between drinks
  3. Switch to low alcohol alternatives
  4. Avoid salty snacks such as peanuts, as they make you more thirsty leading you to consume more alcohol
  5. Space out your drinks along with lots of food
  6. Watch out for peer-pressure and avoid any triggers
  7. Don't be shy to reach out for support

Do you have your DNA raw data from 23andMe, AncestryDNA, MyHeritage, FTDNA, LivingDNA, etc.?

Upload the file to Xcode Life to get insights into 700+health-related traits!

Updated 05 May 2020

It is hard to believe that caffeine, a stimulant that holds popularity in battling fatigue and improving creativity, can do any harm.

1. Caffeine Sensitivity

Caffeine sensitivity is a term that describes the efficiency of the human body to process caffeine and to metabolize it.

We have all heard of co-workers who drink 6 cups of coffee, the recreational drink for nearly 60% of Americans, every day, and friends who guzzle a cup an hour before bedtime.

Yet there are some of us who feel jittery, anxious, or even restless after a single cup.

So, is caffeine a scourge, a tonic, or a mix of both?

Is coffee good for you?

For starters, coffee has a few benefits.

A large research study showed that Americans get more antioxidants from coffee than from any other dietary source.

Other studies have shown that there are several nutrients in a cup of brewed coffee, like Magnesium, Niacin, and Potassium, depending on the soil nutrients and the type of processing.

2. How caffeine works

Adenosine is an organic compound that inhibits arousal and promotes sleepiness upon binding to its receptor.

Caffeine has a structure similar to adenosine and works as an adenosine receptor antagonist.

It competes with adenosine to bind to the adenosine receptor.

This process promotes wakefulness.

Though this can affect the quality of sleep among certain people, it could help in situations like driving at night or averting jet lag, where mental alertness is critical.

Analyze Your Genetic Variants For Caffeine Sensitivity

According to the U.S. Food and Drug Administration (FDA), 300 milligrams of caffeine are consumed every day by the average American. The Mayo Clinic states that drinking up to 400 milligrams per day is safe, which is approximately 4 cups.

A good cup of coffee is the most popular caffeine delivery mechanism that comes with a few health benefits like being a good source of antioxidants, warding off liver disease, and protecting against Parkinson’s.

The health risks and benefits have been understood, over the years, however, caffeine and metabolism, or the way in which our body processes the chemical, varies on several key factors.

3. Caffeine content in popular beverages

BeverageCaffeine content (mg)
Coffee8 oz cup - 95 mg
Espresso1 oz shot - 63 mg
Green tea8 oz cup - 28 mg
Black tea8 oz cup - 26 mg
Energy drinks8 oz cup - 91 mg
Sodas (Cola)16 oz cans - 49 mg
Coffee liqueur1.5 oz shot - 14 mg
Dark chocolate1 oz square 24 mg

4. Caffeine Metabolism: What CYP1A2 gene says

Caffeine, an alkaloid, is also known as  1,3,7-trimetilksantin.

It is acidic in its pure crystalline form and is found in over 60 plant species.

The enzyme CYP1A2 is responsible for the metabolism of caffeine in the liver.

Due to potentially ineffective CYP1A2 enzyme activity, some people can experience issues like caffeine jitters after 2-3 cups of coffee per day.

Such slower metabolizers of caffeine may experience problems with blood pressure, headaches, etc.

Learn More

<strong>Coffee and <em>CYP1A2</em>: 3 ways high caffeine intake can affect you!</strong>

5. More about the CYP1A2 gene

The CYP1A2 gene regulates the synthesis of the enzyme, and small variations in this gene have an association with the efficiency of caffeine metabolism.

Some people have a genetic predisposition to produce very little of CYP1A2 enzyme while others may produce a large amount.

Approximately 10% of the population is found to be rapid caffeine metabolizers, which rates them high on caffeine sensitivity.

Analyze Your Genetic Variants For Caffeine Sensitivity

Approximately 10% of the population are found to be rapid caffeine metabolizers, which rates them high on caffeine sensitivity.

6. Slow metabolizer variant

The polymorphism associated with caffeine metabolism is rs762551.

Studies have shown that individuals with AC or CC genotypes are slow metabolizers of caffeine.

These individuals have a high caffeine sensitivity.

They tend to have a slightly increased risk for heart attack upon consumption of more than 2 cups of coffee every day.

7. Rapid metabolizer variant

Individuals who have the A.A. genotype in the specific polymorphism of the CYP1A2 gene may be fast metabolizers.

These individuals have a low caffeine sensitivity.

study conducted on 553 individuals found that people with this genotype had a 70% reduction in the risk of a heart attack on increased caffeine consumption.

8. How many cups of coffee should you consume? Genetic testing for Caffeine metabolism

The polymorphism in the CYP1A2 gene is well studied and is useful to determine the caffeine metabolism status.

This, in turn, can shine some light on the tendency to consume caffeine. 

9. 23andMe caffeine results

The 23andMe reports provide caffeine metabolizer status.

There are other well known 23andMe third-party tools, like Xcode Life, that can provide a better understanding.

Upload your 23andMe raw data to find out your caffeine metabolism status.

[table id=44 /]

23andMe DNA raw data is the genetic information obtained after a genetic test, and it is usually provided as a text file.

This information can be downloaded after utilizing the 23andMe login provided to all 23andMe customers.

10. Using your Ancestry DNA raw data to identify your caffeine metabolizer status

There is a wealth of information provided by ancestry DNA that can be used to identify a number of health and nutrition-based traits.

Use your ancestry DNA login to download your Ancestry DNA raw data.

You can then upload your Ancestry DNA raw data onto our site to identify the caffeine metabolizer status.

11. 23andme vs. AncestryDNA vs. Xcode Life

23andme vs. AncestryDNA vs. Xcode Life pertaining to caffeine metabolizer status

[table id=45 /]

12. Your genetic predisposition to consume caffeine

People of certain genetic types tend to have a genetic predisposition to drink more cups of coffee.

Identification of this tendency will help in moderating coffee consumption, taking into account the caffeine metabolism status of the individual.

Genetic tests can help identify such parameters.

After all, it would be good to know if you are prone to guzzling down a little too much, especially when your caffeine sensitivity scale is tipped at the wrong end.

Updated on 10 June, 2020

ACE gene: An introduction

ACE gene codes for Angiotensin-Converting Enzyme.

This enzyme is a part of the Renin-Angiotensin System, which is responsible for maintaining blood pressure, and fluid and salt balance in the body.

The enzyme cleaves the protein angiotensin I at a particular site, converting it into angiotensin II.

This angiotensin II brings about constriction of blood vessels, thereby increasing the blood pressure.

ACE gene is located on the long arm of chromosome 17.

Mutations in the ACE gene have been associated with a severe form of the renal disease called renal tubular dysgenesis.

What are ACE inhibitors? 

As the name goes, ACE inhibitors are medications that slow down or inhibit the effects of angiotensin-converting enzyme (ACE).

Such medications are involved in relaxing the blood vessels and reducing blood pressure levels.

They are primarily used as anti-hypertensive drugs.

The ACE inhibitors prevent the angiotensin-converting enzyme from producing angiotensin II.

This reduces blood pressure and makes it easier for the heart to pump blood, thereby improving the functioning of the heart.

ACE inhibitors can be used to treat the following conditions:

Common examples of ACE inhibitors are:

What are the side effects of ACE inhibitors? 

Like any other medication, ACE inhibitors too, have a few side effects. But, most of them are not a cause of worry.

These include:

ACE inhibitors and weight loss 

According to a study conducted by researchers in Australia, it was observed that ACE deficient mice weighed 20% lesser than the mice with ACE activity. It was also observed that the ACE deficient mice had 50% less body fat, especially around the belly area. 

The results from this study have suggested that ACE inhibitors might help in weight loss around the mid-section in humans.

This, along with the other effects of ACE inhibitors, might be cardio-protective.

Handpicked article for you: Is Dr. Rhonda Patrick Diet For You? Analyze Your DNA Raw Data To Find Out Your Nutritional Needs!

Are ACE inhibitors safe for the kidneys? 

ACE inhibitors are cardio and renoprotective.

They reduce systemic vascular resistance in patients with hypertension, chronic renal disease, and heart failure.

ACE inhibitors as we know by now cause a fall in the blood pressure.

Intrarenal efferent vasodilation is also observed along with a fall in the glomerular filtration pressure.

These events are said to be renoprotective.

However, when the glomerular filtration is critically dependent on the angiotensin II-mediated efferent vascular tone, giving ACE inhibitors to the patient can induce acute renal failure.

The systemic and renal hemodynamic consequences, both benefits and adverse effects, are brought about by the depletion of sodium. 

Treating such patients with diuretics and ACE inhibitors, along with some sodium intake restrictions, can improve their therapeutic efficiency.

So, if the patients have a high risk of adverse renal effects to ACE inhibitors, their dosages should be titrated appropriately, and renal function and potassium levels should be closely monitored.

ACE inhibitors vs. beta-blockers 

ACE inhibitors and beta-blockers are both classes of drugs that are used to treat hypertension.

Though their goal is the same, their mechanism of action is entirely different. 

ACE inhibitors work by preventing the conversion of angiotensin I to angiotensin II.

Thus, they cause the relaxation of blood vessels and lower the blood pressure.

Beta-blockers, on the other hand, block epinephrine (adrenaline) and norepinephrine (noradrenaline) from binding to beta receptors on the nerves.

This reduces the heart rate and subsequently lowers blood pressure.

Both these classes of drugs have their side effects and drawbacks.

In most cases, a combination of one or more anti-hypertensive drugs is used to treat high blood pressure.

What is hypertension? 

Hypertension is a widespread and highly prevalent lifestyle disease.

It is a medical term given for consistently high blood pressure over 120mm Hg systolic and 80mm Hg diastolic.

Hypertension is characterized by the flow of blood at high pressure against the walls of the blood vessels. 

As a result, the workload of the blood vessels and the heart increases substantially.

Over a period of time, this force and friction on these tissues end up damaging them, and this can precipitate many conditions.

Some of them include:

What are the leading causes and symptoms of hypertension? 

Hypertension can be of two types: Primary and secondary.

When the rise in blood pressure levels is due to a non-identifiable cause, it is known as primary hypertension.

However, when there is an increase in the blood pressure levels due to an underlying condition, it is called secondary hypertension.

Some common causes of hypertension include:

Though hypertension is often silent, in some cases, the patient does show some symptoms. Like:

What are the four stages of hypertension? 

[table id=124 /]

Individuals who are in the prehypertension stage can progress to the other stages if immediate action is not taken.

Untreated cases of hypertension can even be fatal.

Diet recommendations to reduce blood pressure

One of the primary causes that result in hypertension is poor lifestyle choices, which includes an unhealthy diet.

So, to reduce the blood pressure levels and maintain it under the limit, certain dietary recommendations should be followed.

What is the DASH diet? 

DASH diet is an acronym for Dietary Approaches to Hypertension diet.

The plan includes adopting a diet which includes fruits, vegetables, whole grains, low-fat dairy, nuts and seeds, legumes, fish, and poultry.

The most important aspect is to eat foods that are rich in potassium, calcium, magnesium, protein, and fiber and avoiding foods rich in sodium.

DASH diet is low salt and low sugar diet that does not allow the intake of desserts, sweetened drinks and beverages, red meat, and processed meats and fats.

The diet allows a maximum of 2000 calories a day, which includes:

  1. 7-8 servings of grains
  2. 4-5 servings each of fruits and vegetables
  3. 2-3 servings of low-fat or fat-free dairy products
  4. 1-2 servings of lean meat or fish 
  5. 4-5 servings of nuts and seeds per week
  6. 2-3 servings of oil or fat 
  7. Not more than five servings of sweets per week 

Can high blood pressure be cured?

In most cases of primary hypertension, blood pressure levels can be brought down by a combination of medications, dietary changes, regular exercise, and lifestyle modifications.

Once the blood pressure has been controlled, the individual can maintain his/her blood pressure levels within a reasonable range by living and eating healthy.

In many cases, a precautionary medication is advised to prevent the blood pressure from shooting up. 

Salt intake and high blood pressure 

Our kidneys are responsible for water and salt regulation.

More the salt we consume, more the kidneys tend to retain water.

The increased water retention results in an increase in our systemic blood pressure.

This leads to increased pressure on the walls of many blood vessels, which may result in organ damage. 

ACE gene and hypertension 

Of the many factors that can cause hypertension, the ACE gene also plays a role.

We know that the blood pressure in the body is controlled by the kidneys.

But, to be more specific, the Renin-Angiotensin System or RAS system is responsible for regulating it.

Some genetic variations are related to the RAS system, the most common one being the insertion/deletion polymorphism of the ACE gene.

So, essentially, the interactions between the ACE I/D polymorphism, sodium intake the RAS system determine your blood pressure and influence the risk of developing hypertension.

rs2106809

It was observed that the DD genotype of ACE and the TT genotype of ACE2 were significantly high in female hypertensives and the T allele of ACE2 was also linked to male hypertensives.

[table id=123 /]

rs4308

SNP rs4308 is located on chromosome 17.

Presence of the A allele is responsible for the increase in the diastolic blood pressure.

This SNP locus also features as a target of anti-hypertensive drugs.

ACE gene and fitness 

The ACE gene has been linked to athletic performance.

A genetic variation consisting of 287 DNA bases when inserted into the ACE gene causes a decrease in the ACE enzyme activity.

This version of the gene is called the ‘I’ version.

This variation is shown to be present in athletes, especially sprinters.

The presence of this insertion has been seen in many athletes who perform well in endurance sports such as wrestling, swimming, triathlons, etc.

Though the exact mechanism of how the ACE I gene contributes to fitness and athleticism is unknown, it probably has something to do with an increase in the heart rate, blood pressure, and muscle growth during training.

rs4343

SNP rs4343 of the ACE gene has the ‘A’ and ‘G’ allele.

The A allele is associated with the insertion or I variation, whereas the G allele of the gene is associated with deletion or the D variation.

The G allele results in an increased risk of heart disease (GG) whereas, the minor A allele shows an increased association with endurance-based athletes. 

SNP rs4343 has also recently been linked to susceptibility to migraine, where a G/G polymorphism was seen in patients with migraine with aura as compared to patients of migraine without aura.

Does your 23andme, Ancestry DNA, FTDNA raw data have ACE gene variant information?

CHIP VersionVDR SNPs
23andMe (Use your 23andme raw data to know your ACE Variant)
v1 23andmePresent
v2 23andmePresent
v3 23andmePresent
v4 23andmePresent
V5 23andme (current chip)Present
AncestryDNA  (Use your ancestry DNA raw data to know your ACE Variant)
v1 ancestry DNAPresent
V2 ancestry DNA (current chip)Present
Family Tree DNA  (Use your FTDNA raw data to know your ACE Variant)
OmniExpress microarray chipPresent

References:

  1. https://ghr.nlm.nih.gov/gene/ACE#synonyms
  2. https://www.ncbi.nlm.nih.gov/pubmed/8879974
  3. https://www.ncbi.nlm.nih.gov/pubmed/17473847?dopt=Abstract
  4. https://www.ncbi.nlm.nih.gov/pubmed/24112034
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972004/
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